Guillain Barre syndrome (AIDP), Miller Fisher syndrome, CIDP Flashcards
(16 cards)
Guillain-Barré Syndrome (GBS) is acute autoimmune polyradiculoneuropathy. It is characterised by rapid progressive, symmetrical ascending lower motor neuron muscle weakness.
It progresses over days to 4 weeks.
Clinical variants of GBS:
1. Acute inflammatory demyelinating polyneuropathy (AIDP)
2. Acute motor axonal neuropathy (AMAN)
3. Acute motor and sensory axonal neuropathy (AMSAN)
4. Miller Fisher syndrome (MFS)
5. Bickerstaff brainstem encephalitis (BBE)
Pathophysiology of GBS
- Triggers 1-3 weeks prior to onset:
- Campylobacter jejuni gastroenteritis
- CMV and EBV
- Mycoplasma pneumoniae
- Influenza virus
- Zika virus
- Surgery, trauma, vaccination - Humoral immunity - B cells produce antibodies against gangliosides (GM1) or neural antigens that bind on peripheral nerves.
- Cellular immunity - T cells release cytokines and facilitate B cell activation.
- Complement activation and cascade leading to membrane attack complex (MAC) damaging myelin and axons.
- Macrophage invades nerves, phagocytosis of myelin and also causes axonal damage.
- Patterns of immune attack
- Myelin: demyelination (of myelin sheath) causing conduction block
- Axon: axonal degeneration
- Acute inflammatory demyelinating polyneuropathy (AIDP)
- Pathology: primary demyelination
- Demographics: North America and Europe.
- Pattern: ascending paralysis, sensory symptoms and areflexia. - Acute motor axonal neuropathy (AMAN)
- Pathology: axonal damage
- Demographics: East Asia, Latin America. Due to c-jejuni infection with anti-GM1 antibodies
- Pattern: pure motor ascending paralysis - Acute motor and sensory axonal neuropathy (AMSAN)
- Similar pathology and demographic to AMAN with sensory involvement - Miller-Fisher syndrome (MFS)
- Expresses anti-GQ1b antibodies
- Triad of: ophthalmoplegia, ataxia, areflexia (OAA), may or may not have limb weakness - Bickerstaff brainstem encephalitis
- MFS + coma / altered consciousness
Clinical presentation of patients with GBS
- Antecedent event up to 1 month ago - gastroenteritis
- Motor symptoms
- Distal: fine movement impaired
- Proximal: difficulty getting up, walking - Possible sensory numbness or pain
- Cranial nerve involvement
- CN7: facial weakness, droop
- CN9, 10, 12: dysphagia, dysarthria, aspiration
- CN3, 4, 6: ophthalmoplegia - diplopia, ptosis - Autonomic dysfunction
- Tachycardia, bradycardia, arrhythmias
- Labile blood pressure (hypo/hypertension)
- Orthostatic hypotension - Respiratory failure
- Diaphragm or intercostal muscle weakness
Examination findings/clinical signs of GBS
Inspection
1. Appears weak, lethargy
2. Respiratory - dyspnoea, accessory muscle use
3. Weak voice
4. Altered mental status (BBE - not in PACES)
Cranial nerve examination
1. CN3, 4, 6 - complex ophthalmoplegia
2. Pupils - sluggish, mydriasis or miosis
3. Possible mild CN5 paraesthesia and mastication deficit
4. LMN CN7 unilateral or bilateral facial weakness
- Forehead affected, weak eyebrows, weak puffing cheek
- Incomplete eye closure
- Asymmetrical smile
- Loss of anterior 2/3 tongue taste sensation
5. CN 9, 10, 12 - bulbar weakness
- Tongue fasciculation and weakness
- Dysphagia, dysarthria
- Absent gag reflex
- Autonomic dysfunction - arrhythmias, labile BP
6. CN 11 - SCM and trapezius weakness
UL or LL examination
1. Lower motor neuron muscle weakness
- Hypotonia, hypo/areflexia, Babinski absent
- Muscle weakness
2. Ascending weakness - from lower limbs to trunk, upper limbs and cranial nerves
(watch out for variant patterns - descending, arm-predominant)
3. Possible reduced spinothalamic or DCML sensation loss in gloves/stocking distribution
4. Ataxia - in MFS; or due to weakness
5. Gait - unsteadiness, ataxic, foot drop
Complications
1. Sphincter (bladder, bowel) dysfunction
1. Respiratory failure
3. Cardiac arrhythmias
4. Vitals - labile BP and HR
Summary findings of GBS
- Symmetrical, LMN, ascending motor weakness
- Hypotonia, hypo/areflexia
- Possible sensory deficit
- Possible cranial nerve involvement (CN 3, 4, 6, 7, bulbar)
- Signs of autonomic dysfunction
Diagnostic investigations for GBS
- Lumbar puncture for CSF analysis
- Albuminocytologic dissociation (elevated CSF protein, normal WBC count) - NCS and EMG
- Conduction block, reduced amplitude - Anti-GM1 or GQ1b antibodies
- MRI brain and spine
- Infective screening: c jejuni, CMV, EBV, HIV
Management of GBS
MDT - Neurology, PT, OT, ST, dietitian, ICU
- Critical care
- Respiratory care: NIV or intubation
- DVT prophylaxis - Supportive
- Nutritional support
- Bladder and bowel care - IVIg - 0.4g/kg/day for 5 days (total 2g/kg)
- PLEX - 4-6 exchanges (200-250mL/kg) over 1-2 weeks
DO NOT administer steroids
Prognosis of GBS
Mortality: 3-7%
- Causes: respiratory failure, sepsis, pulmonary embolism, autonomic dysfunction
Recovery: 80-85% good recovery, ambulate independently by 6-12 months
Recurrence: 2-5% (rare)
Long term sequelae
1. Persistent distal weakness (foot drop, hand weakness)
2. Chronic fatigue and pain
3. Sensory disturbance
4. Reduced exercise tolerance
5. Psychological (anxiety, depression, PTSD)
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic acquired autoimmune polyradiculoneuropathy. Inflammation and demyelination of peripheral nerves result in progressive or relapsing-remitting weakness and sensory loss.
It occurs over more than 8 weeks.
Pathophysiology of CIDP
- Differing antibodies from AIDP
- Anti-NF155, anti-CNTN1, anti-CASPR1 - T-cells, B-cells, macrophage and complement activity against peripheral nerves
- Demyelination and remyelination (onion bulbs formation)
Clinical presentation of patients with CIDP
- Subacute to chronic onset (8 weeks or more)
- Slow progressive: gradual worsening over months to years
- Relapse-remitting: repetitive worsening and partial recovery - LMN motor weakness (proximal > distal)
- Hypotonia, hyporeflexia/areflexia
- Proximal: difficult climbing stairs, getting up, lifting arms
- Fatigue - Sensory problem
- Positive symptoms: neuropathic pain (burning, shooting), musculoskeletal pain
- Negative symptoms: paresthesia, DCML loss - Milder CN involvement (ophthlamoplegia, facial weakness, bulbar palsy)
- Mild or no autonomic dysfunction
Clinical variants of CIDP
- (similar but distinct) Multifocal motor neuropathy
- Progressive, asymmetrical distal weakness without sensory loss
- NCS/EMG: conduction block
- Responds to IVIg (unresponsive to steroids) - Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM)
- Asymmetric, multifocal weakness and sensory loss (mononeuritis multiplex) of UL or LL
- NCS/EMG: focal demyelination, conduction block
- Responds to IVIg or steroids - Distal acquired demyelinating symmetric neuropathy (DADs)
- Symmetrical, distal sensorimotor deficit, with paresthesia and ataxia
- Associated with MGUS - Pure motor CIDP and pure sensory CIDP
- Difficult to differentiate from motor neuron disease, multifocal motor neuropathy
Diagnostic investigations for CIDP
- NCS/EMG
- Primary demyelination of at least 2 nerves: prolonged latency, reduced velocity - Lumbar puncture with CSF analysis
- Albuminocytologic dissociation: elevated protein (>45g/dL) with normal WBC count - Sural nerve biopsy
- Onion bulb formation
- Mononuclear cell infiltrate - CIDP specific antibody testing
- Anti-NF155, anti-CNTN1, anti-CASPR1
- Anti-MAG
- Anti-GM1 (in MMN) - Screen for MGUS with SPEP and IF
- MRI spine, nerve roots, plexus
- Nerve ultrasound - nerve enlargement
Management of CIDP
Definitive management
1. Corticosteroids
- High dose prednisolone 1mg/kg/day taper slowly
- Pulse IV methylprednisolone
- IVIg - 2g/kg over 2-5 days
- Loading and maintenance infusion - PLEX - 5-10 exchanges over 2-4 weeks
- Steroid sparing agents
- Azathioprine, MMF, MTX, CNI
Supportive care
1. Rehabilitation
2. Neuropathic pain management - gabapentin
3. Foot orthosis
4. Psychological support
